PROJECT SUMMARY Light-driven chemistry (or photoredox catalysis) has made significant advances in the last decade for practical organic or drug synthesis. For example, light-induced reactions have enabled generation of radical intermediate R? for direct functionalization of biologically relevant heterocycles and cross-coupling reactions for important covalent bond formations. Therefore, photoredox catalysis offers tremendous potentials to access novel drug architectures not possible with conventional heat-driven processes, reduce drug synthesis steps, and improve process safety, all of which drastically reduce pharmaceutical manufacturing costs. These benefits have compelled drug companies to invest heavily in incorporating light-driven chemistry to their next generation of pharmaceutical manufacturing. From the public health?s perspective, light-driven chemistry has the potential to substantially lower the cost to access therapeutics to improve overall human health. Dihydrophenazine and phenoxazine organic photoredox catalyst (PC) products, a spin-off innovation from the Miyake lab, are key to enable this photoredox revolution in the pharmaceutical industry. Designed to possess advanced photophysical properties (highly reducing, charge transfer excited state, and redox reversibility), these organic PCs dominate any PCs (precious metals or other organic PCs) in the oxidative quenching applications, where an excited state reductant is required. Specifically, dihydrophenazine and phenoxazine PCs has been demonstrated as cost-effective replacement for precious metal iridium or ruthenium PCs in numerous radical-induced and cross-coupling reactions. In some cases, these organic PCs were shown superior than iridium or ruthenium PCs; for example, they were employed in lower catalyst loading and were used to discover novel chemistry. In this SBIR proposal, a number of technical hurdles associated with organic PCs commercialization will be resolved to de-risk and ensure long term competitiveness of the company. In Aim 1, optimization of synthetic routes was proposed for dihydrophenazine and phenoxazine synthesis to reduce production cost. In Aim 2, using the optimized synthetic routes, the organic PCs production will be scaled up from 10g/ week to 1kg/ week. In Aim 3, to validate the performance of the organic PCs in an industrially relevant environment, the organic PCs will be applied in kg-scale drug intermediate synthesis using a photoflow reactor. The completion of this project will advance the organic PC products from Technology Readiness Level (TRL) 4.5 to 6.